At the university, Motzkin helped found the Russian Jewish Academic Association in 1887 and soon became a full-fledged activist in the Zionist movement.

Motzkin participated in the First Zionist Congress in 1897 and became close to the Zionist leader Theodor Herzl, who sent him on a mission to Palestine to investigate the problems of the Jewish community; contrary to other leaders such as Baron Rothschild and Hovevei Zion, Motzkin favored co-operation with the Ottoman Empire for Jewish interests.

[1] In 1902, together with Martin Buber and Berthold Feiwel, Motzkin founded Berlin's Jüdischer Verlag (Jewish Publishing House).

[1] Leo Motzkin also traveled to the United States to collect funds for Jewish refugees and lobby for the protection of Russian Jews.

[2] Motzkin was an early and leading opponent of the Nazi Party, organizing opposition to it and lobbying the League of Nations to ensure the safety of the German Jewish population.